Usmle Step 1 -- Dit: Heme

Front 1

What test can be used to diagnose B-thalassemia minor?

Back 1

Hemoglobin electrophoresis.

Front 2

You see hypersegmented neutrophils on a peripheral blood smear. What are you thinking?

Back 2

Megaloblastic anemia.

Front 3

What is one cause of megaloblastic anemia that doesn't respond to Vit B12 and folate supplementation?

Back 3

Orotic aciduria.

Front 4

A bone marrow biopsy shows hypocellularity with fatty infiltration. What's the dx? What causes this?

Back 4

Aplastic anemia; radiation and drugs, viral agents, Fanconi's anemia, idiopathic.

Front 5

A patient is diagnosed with macrocytic, megaloblastic anemia. What is the danger of giving folate alone?

Back 5

Correct anemia, but not address B12 def --> pt could get peripheral neuropathy w/o anemia --> you're going to be like "WTF".

Front 6

A patient with sickle cell disease develops osteomyelitis. What is the offending organism?

Back 6

Salmonella.

Front 7

What is the difference between the hemoglobin S and hemoglobin C defect?

Back 7

HbC: glutamic acid-to-lysine mutation at position 6 in β chain.
HbS: glutamic acid-to-valine mutation at position 6 in β chain

Front 8

What enzyme does Warfarin inhibit?

Back 8

Epoxide reductase. No activation of Vitamin K for gamma-carboxylation of glutamate residues on immature clotting factors.

Front 9

Which clotting factor is deficient in Hemophelia A? Hemophelia B?

Back 9

Factor VIII; Factor IX.

Front 10

Why are neonates given a shot of Vit K after birth?

Back 10

They lack the enteric bacteria needed to produce Vit K.

Front 11

What are the effects of bradykinin on the body?

Back 11

Increased vasodilation, increased permeability, and increased pain.

Front 12

What clotting factors are dependent on Vitamin K for synthesis?

Back 12

Factors II, VII, IX, X, Protein C, Protein S.

Front 13

What is the function of Proteins C and S? What is the clinical consequence of a deficiency in Protein C and/or S?

Back 13

Proteins C and S inactivate Va and VIIIa; Hypercoaguable state.

Front 14

What is the defect in Bernard-Soulier disease?

Back 14

Defect in platelets! Decreased Gp1b on platelets = decreased adherence to vWF on endothelial collagen --> no platelet to collagen adhesion.

Front 15

What is the defect in Glanzmann's thrombasthenia?

Back 15

Defect in platelets! Decreased GpIIb/IIIa = no platelet to platelet aggregation!

Front 16

What is the defect in Idiopathic Thrombocytopenic Pupura (ITP)? What might you see on a blood smear?

Back 16

Poor platelet survival! Anti-GpIIa/IIIb antibodies --> peripheral platelet destruction! Increased megakaryocytes on blood smear.

Front 17

What is the defect in Thrombotic Thrombocytopenic Purpura (TTP)?

Back 17

Poor platelet survival! Deficiency in ADAMTS 13 = decreased degradation of vWF multimers = increased platelet aggregation and thrombosis.

Front 18

What's the defect in vonWillebrand's disease?

Back 18

Decreased vWF = defect in platelet-to-collagen adhesion. MOST COMMON INHERITED BLEEDING DISORDER.

Front 19

What can cause DIC? What will you see in the labs?

Back 19

"STOP Making New Thrombi": Sepsis (gram-negative), trauma, obstetric complications, acute pancreatitis, malignancy, nephrotic syndrome, transfusion; Increased fibrin split products (D-dimers), decreased fibrinogen, decreased factors V and VIII.

Front 20

What are the hereditary thrombosis syndromes leading to hypercoaguability?

Back 20

Factor V Leiden, Prothrombin gene mutation, antithrombin deficiency, protein C or S deficiency.

Front 21

What's the defect in Factor V Leiden?

Back 21

Mutant Factor V cannot be degraded by Protein C. MOST COMMON CAUSE OF INHERITED HYPERCOAGUABILITY.

Front 22

What are the treatments for overdose of heparin and warfarin?

Back 22

Protamine sulfate for heparin OD and Vit K +/- FFP for warfarin OD.

Front 23

What lab value is used to monitor heparin? warfarin? enoxaparin?

Back 23

PTT; PT/INR; Xa.

Front 24

What is the MOA for heparin?

Back 24

Supercharges antithrombin! Decreases the action of IIa (thrombin) and Xa.

Front 25

What is the benefit of LMW heparins like enoxaparin?

Back 25

Increased bioavailability, no need to monitor PTT, longer half-life, can be admin SC, acts more on Xa.

Front 26

What is the treatment for heparin-induce thrombocytopenia (HIT)?

Back 26

Lepirudin, bivalirudin --> directly inhibit thrombin.

Front 27

You have to anticoagulate a pregnant woman. Which drug will you give her?

Back 27

Heparin, b/c it doesn't cross the placenta like warfarin.

Front 28

What are the thrombolytics? What is their MOA?

Back 28

Streptokinase, urokinase, tPA (alteplase), and APSAC (anistreplase); Directly or indirectly aid in converting plasminogen --> plasmin, which cleaves thrombin and fibrin clots.

Front 29

When would you use thrombolytics?

Back 29

EARLY MI, EARLY ischemic stroke.

Front 30

How do you treat a thrombolytic toxicity?

Back 30

Aminocaproic acid.

Front 31

Where does fetal erythropoiesis take place?

Back 31

Yolk sac (wks 3-8) --> Liver (wks 6-30) --> spleen (wks 9-28) --> bone marrow (wks 28+).

Front 32

Where does adult erythropoiesis take place?

Back 32

Long bones, pelvis, sternum, ribs, cranial bones, vertebrae.

Front 33

How are the γ chains of fetal hemoglobin different from the β chains of adult hemoglobin?

Back 33

Decreased affinity for 2,3 BPG and increased affinity for O2.

Front 34

What is the average lifespan of an erythrocyte? What gives the erythrocyte its characteristic biconcave shape and flexibility? What is the main energy source for the erythrocyte?

Back 34

120 days; Spectrin! Glucose (it's the ONLY energy source!).

Front 35

You see a teardrop cell on a blood smear. What do you think?

Back 35

Bone marrow infiltration (e.g., myelofibrosis).

Front 36

You see target cells on a peripheral blood smear. What do you think?

Back 36

"'HALT' said the hunter to his TARGET": HbC disease, asplenia, liver disease, thalassemia.

Front 37

You see Howell-Jolly bodies on peripheral blood smear. What do you think?

Back 37

Patient with functional hyposplenia or asplenia (e.g., sickle cell disease or splenic trauma).

Front 38

You see basophillic stippling on a peripheral blood smear. What do you think?

Back 38

"BASte the ox TAIL": Thalassemias, anemia of chronic disease, iron deficiency, lead poisoning.

Front 39

You see schistocytes/helmet cells on a peripheral blood smear. What do you think?

Back 39

DIC, TTP/HUS, traumatic hemolysis.

Front 40

What is the rate-limiting enzyme in heme synthesis?

Back 40

ALA-synthase.

Front 41

What enzyme is affected in lead poisoning? What substrate accumulates?

Back 41

ALA-dehydratase and Ferrochelatase; Protoporphyrin accumulates.

Front 42

What are the sx of lead poisoning?

Back 42

Lead lines on gingivae and epiphyses of long bones, encephalopathy and erythrocyte basophillic stippling, abd colic, sideroblastic anemia, wrist and foot drop.

Front 43

How do you treat lead poisoning?

Back 43

Adults: EDTA, Dimercaprol.
Children: Succimer, Dimercaprol.

Front 44

What enzyme is affected in acute intermittent porphyria? Which substrate accumulates? What are the clinical sx?

Back 44

Porphobilinogen deaminase; Porphobilinogen, ALA accumulate; Sx include RED-WINE COLORED URINE, polyneuropathy, psych problems, acute abd, precipitated by drugs.

Front 45

What are the features of porphyria cutanea tarda? What enzyme is affected? What substrate accumulates?

Back 45

Blistering cutaneous photosensitivity, TEA-COLORED URINE; nuked uroporphyrinogen decarboxylase, uroporphyrin accumulates.

Front 46

What are the main type of microcytic anemia?

Back 46

Iron-deficiency, ACD, thalassemias, lead poisoning, and sideroblastic anemia.

Front 47

What syndrome is associated with iron-deficiency anemia? What are the histological findings?

Back 47

Plummer-Vinson syndrome (ID anemia, atrophic glossitis, esophageal web); Hypochromia, microcytosis seen under the microscope.

Front 48

What are some of the causes of iron-deficiency anemia?

Back 48

Chronic blood loss (GI or menorrhagia), malnutrition/absorption disorders, increased demand (pregnancy). R/O COLON CANCER!

Front 49

What type of mutation is present in β-thalassemia? What does it result in? In which populations is this mutation prevalent?

Back 49

Point mutation in splice sites and promotor sequences --> decreased β-globin synthesis; Mediterranean populations.

Front 50

What test can be done to diagnose β-thalassemia minor? What would be considered a "positive" result.

Back 50

Hb electrophoresis; HbA2 > 3.5%.

Front 51

What type of hemoglobin is increased in both β-thalassemia major and minor?

Back 51

HbF (α2γ2).

Front 52

In which populations is α-thalassemia prevalent? What does a 4 gene deletion result in? 3 gene deletion? 1-2 gene deletion?

Back 52

Asian and African populations; 4 gene deletion = γ4, incompatible with life (causes hydrops fetalis); 3 gene deletion = HbH disease (β4); 1-2 gene deletion results in no significant anemia.

Front 53

Which enzymes does lead inhibit? What is the genetic disease with the same pathogenesis?

Back 53

Ferrochelatase and ALA dehydratase --> inhibits heme synthesis; Sideroblastic Anemia --> defect in the ALA gene --> defect in heme synthesis --> ringed sideroblasts in the bone marrow!

Front 54

What is the cause of megaloblastic anemia with peripheral neuropathy? What bug might cause this? What are other possible causes?

Back 54

B12 deficiency; Diphyllobothrium latum; malabsorption (Crohn's), strict vegan diet, pernicious anemia.

Front 55

What type of anemia is commonly seen in alcoholics?

Back 55

Megaloblastic anemia caused by Folate deficiency.

Front 56

What could be the cause of a megaloblastic anemia in an HIV+ patient?

Back 56

Zidovudine.

Front 57

What would cause a megaloblastic anemia refractive to tx w/Vit B12 and folate, but that is reversible with Vit B6?

Back 57

Orotic aciduria.

Front 58

What type of labs would you see with ACD?

Back 58

Decreased Iron, Decreased TIBC (it's just not being used), Increased Ferritin.

Front 59

What is the mutation responsible for Sickle Cell Hb (HbS)? What is the mutation responsible for HbC?

Back 59

Glutamate --> Valine in β chain.
Glutamate --> Lysine in β chain.

Front 60

What disease has a characteristic "crew cut" appearance on x-ray?

Back 60

Sickle cell anemia.

Front 61

What is the defect in hereditary spherocytosis? What are the findings? Tx?

Back 61

Defect is in ankyrin or spectrin -- loss of characteristic discoid shape to RBC --> premature removal of RBCs by spleen; splenomegaly, jaundice, pigmented gallstones!, aplastic crisis (if infected with B19), Howell-Jolly bodies after splenectomy; Tx is splenectomy

Front 62

What is the defect in pyruvate kinase deficiency anemia?

Back 62

Defect in pyruvate kinase --> decreased ATP --> rigid RBCs --> hemolytic anemia in the newborn.

Front 63

Impaired synthesis of what molecule is responsible for paroxysmal nocturnal hemoglobinuria?

Back 63

CD55 or CD59 (GPI anchor/decay-accelerating factor in RBC membrane) --> prevents complement-mediated RBC lysis!

Front 64

What types of complications are seen in patients with HbSS?

Back 64

Aplastic crisis, autosplenectomy, increased risk of infection with encapsulated bugs, SALMONELLA OSTEOMYELITIS, painful crisis, renal papillary necrosis.

Front 65

What are the findings of extravascular hemolysis?

Back 65

Macrophages in spleen clear the RBCs: increased LDH, increased UCB --> jaundice.

Front 66

What are the features of intrinsic hemolysis?

Back 66

Decreased haptoglobin, increased LDH, hemoglobinuria.

Front 67

What type of Ig is involved in warm agglutinin AIHA? Cold agglutinin AIHA?

Back 67

IgG; IgM.

Front 68

What is an example of a potentially deadly warm agglutinin AIHA? What test is used to detect the possibility of this occurring?

Back 68

Erythroblastosis fetalis. INDIRECT Coombs' test will be POSITIVE.

Front 69

What will you see on a blood smear of a patient with microangiopathic anemia? Where is this pathology seen?

Back 69

Shistocytes (Helmet cells) -- d/t mechanical destruction of RBCs; Seen in DIC, TTP-HUS, SLE, malignant HTN.

Front 70

What causes macroangiopathic anemia?

Back 70

Prosthetic heart valves and aortic stenosis --> mechanical destruction of RBCs + schistocytes on peripheral blood smear.

Front 71

What bugs chomp up RBCs?

Back 71

Plasmodium spp. (malaria) and Babesia.

Front 72

What drug can improve the sx of sickle cell disease? What is the mechanism of this drug?

Back 72

Hydroxyurea; Inhibits ribonucleotide reductase but also STIMULATES HbF PRODUCTION!!.

Front 73

Cold agglutinins are nearly always seen in which infections?

Back 73

Mycoplasma pneumoniae and EBV.

Front 74

Who carries around vWF in the blood? Where else is vWF found?

Back 74

Factor VIII; endothelial cells of blood vessels.

Front 75

What causes ITP?

Back 75

Auto-antibodies to GpIIb/IIIa --> decreased platelet survival.

Front 76

What is the defect in Bernard-Soulier disease?

Back 76

Deficient GpIb --> poor platelet to collagen adhesion.

Front 77

What is the lifespan of a platelet?

Back 77

8-10 days.

Front 78

What molecule is expressed on the surface of a platelet after it becomes activated? To what does this molecule bind?

Back 78

GpIIb/IIIa; binds fibrinogen, which links it to another platelet GpIIb/IIIa.

Front 79

What is the mechanism of action for Clopidogrel and Ticlopidine? SE?

Back 79

Inhibits platelet aggregation by blocking the platelet's ADP receptor --> prevents expression of GpIIb/IIIa --> no binding to fibrinogen --> no linking to other platelets --> no aggregation; NASTY BONE MARROW SUPPRESSION.

Front 80

What is the clinical use for Clopidogrel and Ticlopidine?

Back 80

Acute coronary syndrome, coronary stenting.

Front 81

What is the mechanism of action for Abciximab? What's the indication?

Back 81

Monoclonal antibody to GpIIb/IIIa --> binds GpIIb/IIIa on activated platelets --> prevents platelet aggregation; acute coronary syndromes, particularly NON-STEMIs.

Front 82

What structure is pathognomonic for a MYELOID leukemia?

Back 82

Auer Rods.

Front 83

What are faggot cells? What are they pathognomonic for? What is the chromosomal abnormality in this disease?

Back 83

Blasts with stacks of Auer rods; Pathognomonic for AML--M3; t(15;17).

Front 84

What is used to treat AML-M3? What is the risk associated with tx of AML-M3?

Back 84

all-trans retinoic acid (vitamin A) --> matures myeloblasts. If this isn't done, lysis of the myeloblasts will release auer rods, which can elicit DIC.

Front 85

Which type of disorder has cells that are CD13 and CD33 + and is PAS - ? Who is at increased risk for developing this dx?

Back 85

AML; patients with myeloproliferative disease, myelodysplastic syndrome, aplastic anemia, Down syndrome, Fanconi syndrom, or Bloom syndrome.

Front 86

What is the name for peroxidase-positive cytoplasmic inclusions in granulocytes and myeloblasts? Which disease do you see these in? What is the average age of onset?

Back 86

Auer rods. AML (2-3). 50 yrs old.

Front 87

Greater than 20% blasts in the bone marrow is the cut-off for diagnosing this disease.

Back 87

AML.

Front 88

What is the chromosomal abnormality in the most common leukemia of U.S. adults? Which genes is it always associated with? What do these genes encode for? What is the tx?

Back 88

Philadelphia chromosome: t(9;22); bcr-abl genes; bcr-abl encodes for a mutant tyrosine kinase receptor that is constitutively active; Tx is Imatinib.

Front 89

The disease shows hyperplasia of all three cell lines (granulocytic, erythroid, and megakaryocytic), but granulocyte precursors predominate.

Back 89

CML.

Front 90

What is the average age of onset for CML? What are the presenting sx? What cell will you see under the microscope that will make you shout "CML! CML!"?

Back 90

25-60 years old; Sx: fatigue, abdominal pain, splenomegaly, bleeding tendency; BASOPHILS.

Front 91

This is the most common leukemia in children, often presents with bone pain, and cells are PAS +.

Back 91

ALL.

Front 92

A 11 y/o male presents with bone pain and a mediastinal mass; cytology reveals TdT+ cells. What is the diagnosis? What chromosomal alteration gives him a better prognosis?

Back 92

ALL; t(12;21).

Front 93

What congenital syndrome is ALL associated with?

Back 93

Down Syndrome.

Front 94

Who gets SLL/CLL? What are the presenting sx? What will you see on a peripheral blood smear? What other pathological process goes on?

Back 94

People >60 yrs old; Often asymptomatic; SMUDGE CELLS under the microscope; Warm antibody (Which isotype?...IgG!) autoimmune hemolysis.

Front 95

What's the difference between SLL and CLL?

Back 95

They are the same, but CLL has increased peripheral blood lymphocytes.

Front 96

You see a cell under the microscope with filamentous, hairlike projections. It stains TRAP+. What is it? Who has it?

Back 96

Hairy cell leukemia; Adults and elderly.

Front 97

What are the chronic myeloproliferative disorders? Which mutation is common to all of them but one? Which one doesn't have this mutation?

Back 97

Polycythemia vera, Essential thrombocytosis, Myelofibrosis, CML; JAK2 mutation (hematopoietic growth factor signaling); CML.

Front 98

What type of Ig is overproduced in multiple myeloma? What will you see on x-ray? What will you see on protein electrophoresis? What will you see on a blood smear? UA?

Back 98

IgG (55%) and IgA (25%); punched-out lytic bone lesions on x-ray; M spike; Numerous plasma cells with "clockface chromatin" and intracytoplasmic inclusions containing Ig, also rouleaux formation; Bence Jones proteins (Ig LIGHT CHAINS) in urine.

Front 99

What are the presenting sx of multiple myeloma?

Back 99

"CRAB": hypercalcemia, renal insufficiency, anemia, bone lytic lesions/back pain.

Front 100

What are some toxic changes you will see in a leukemoid reaction?

Back 100

Granulocytosis, vacuoles, Dohle bodies.

Front 101

What cellular finding makes for a better prognosis in Hodgkin lymphoma?

Back 101

Increased lymphocyte to Reed-Sternberg cell ratio.

Front 102

What type of Hodgkin lymphoma will you find lacunar cell variants of the Reed-Sternberg cell?

Back 102

Nodular sclerosing.

Front 103

What type of cell does the R-S cell originate from? What are its cell surface markers?

Back 103

B cell; CD30+ and CD15+

Front 104

In what type of lymphoma will you see mediastinal involvement, constitutional sx, and an association with EBV infection?

Back 104

Hodgkin lymphoma.

Front 105

Which type of lymphoma is associated with multiple, peripheral node involvement, extranodal involvement and noncontiguous spread?

Back 105

Non-Hodgkin lymphoma.

Front 106

What is the most common adult non-Hodgkin lymphoma?

Back 106

Diffuse large B-cell lymphoma.

Front 107

What is the chromosomal abnormality in Burkitt's lymphoma? What gene is this associated with? What infection is Burkitt's lymphoma associated with?

Back 107

t(8;14); c-myc gene (moves next to heavy Ig chain gene, 14); EBV infection.

Front 108

Who gets Burkitt's lymphoma? What does it look like under the microscope?

Back 108

Adolescents or young adults; STARRY SKY appearnace -- sheets of lymphocytes with interspersed macrophages.

Front 109

What is the genetic defect in mantle cell lymphoma? What gene is associated with this?

Back 109

t(11;14); DEACTIVATION of Cyclin D regulatory gene --> cell progresses through cell cycle uninhibited.

Front 110

Who gets follicular lymphoma? What is the genetic defect in this disease? What gene is associated with this?

Back 110

Adults; t(14;18); bcl-2 expression --> inhibits apoptosis. Poor prognosis.

Front 111

Who gets adult T-cell lymphoma? What causes this?

Back 111

Adults in Japan, West Africa, and Caribbean populations; HTLV-1 infection. Present with cutaneous lesions.

Front 112

How does Mycosis fungoides/Sèzary syndrome present? What do the cells look like?

Back 112

Adults present with cutaneous patches/nodule; Under the microscope the patient's blood will show CEREBRIFORM cells! Little brains!